Application of 32 Factorial D-Optimal Design in Formulation of Porous Osmotic Pump Tablets of Ropinirole; An Anti-Parkinson’s Agent

Abstract

: Objective: In the present study, our objective was to develop porous osmotic pump tablets of an anti-Parkinson’s agent, ropinirole. It also aimed to demonstrate the applicability of factorial designs and there by a statistical optimization in developing a controlled drug releasing device. Methods: A 32 factorial D-optimal study design was adopted to identify an optimized formulation. Tablets were prepared by direct compression using varying amounts of microcrystalline cellulose (MCC) and sodium chloride, followed by coating with semipermeable membrane of cellulose acetate (CA) containing polyethylene glycol (PEG) 400 as a pore former. The plasticity of the membranes was adjusted using castor oil. All the formulations were evaluated for various physical parameters including in vitro drug release and the effect of osmogent and pore former were also studied. Drug release kinetics studies such as zero order, first order and Korsmeyer Peppas were carried out and compared. ANOVA in drug release of all the formulations were determined. Formulations were optimized by using numerical optimization technique to achieve a controlled zero order release of ropinirole for 12 hours. Results: Drug release from the optimized formulation containing 20%w/w of PEG, without osmogent was not significantly affected by change in pH or agitation of the dissolution medium. The mechanism of drug release was further confirmed by studying the effect of osmotic pressure on drug release. Conclusion: The porous osmotic pump tablets of ropinirole can provide prolonged, controlled and GI environment-independent drug release. A software based optimization is helpful and reliable in developing porous osmotic pump tablets.Key words: Osmotic pump, Ropinirole, Controlled release, Factorial design, D-optimal design, Optimization.